Is PEX5 p.Val227fs (c.677dup) pathogenic?

PEX5 p.Val227fs (c.677dup) is classified Pathogenic in PEX5 (ClinVar, Single submitter, 2 submitters; last evaluated 2015-05-15). No gnomAD frequency available for this variant; Associated with rhizomelic chondrodysplasia punctata.

What condition is associated with PEX5 p.Val227fs (c.677dup)?

PEX5 p.Val227fs (c.677dup) is associated with rhizomelic chondrodysplasia punctata, rhizomelic chondrodysplasia punctata type 5 (ClinVar).

How common is PEX5 p.Val227fs (c.677dup) in the general population?

PEX5 p.Val227fs (c.677dup) is no gnomAD frequency available for this variant (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PEX5 p.Val227fs

c.677dup · rs796051881 · VCV190410

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

rhizomelic chondrodysplasia punctata

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX5
Protein: p.Val227fs
Coding: c.677dup
MANE Select: NM_001351132
dbSNP: rs796051881
Type: Duplication
Location: chr12:7202274 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB

Full PEX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

rhizomelic chondrodysplasia punctata — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhizomelic chondrodysplasia punctata type 5

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PEX5 p.Thr316fs Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Val227Ala Uncertain significance ★★ ⚠ same residue
PEX5 p.Leu607fs Likely pathogenic ★ same condition
PEX5 p.Val227= Likely benign ★ same residue
PEX5 c.135_147+33delinsC Likely pathogenic ★★ same condition
PEX5 c.967-1G>A Likely pathogenic ★★ same condition
PEX5 p.Arg420Ter Pathogenic ★★ same condition
PEX5 p.Arg427Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pex5-p-val227fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown